1. The background of the invention pertains to the field of medical radioimaging; specifically, the radioimaging of amyloid proteins in biological organisms such as human patients using a Technecium isotope (99mTc) for radiolabeling congo red. The present invention discloses multiple 99mTc-labeled congo red complexes and their precursors utilizing various diamide dithiolate ligand systems and disclosing convenient methods for making these products, thereby providing a cost effective and practical means for enhancing the radioimaging of amyloid by standard nuclear medicine techniques.
2. Description of the Prior Art
Amyloidosis is a term applied to a group of disorders (e.g. chronic inflammatory diseases, infections, and neoplasms) associated with the deposition of insoluble fibrillar proteins within various organs of the body, which results in significant morbidity and mortality. There are other diseases such as Alzheimer""s disease that are associated with nonsystemic, organ specific amyloid deposits. Before radioimaging, the only practical means for diagnosing amyloid in the tissues was by tissue biopsy.
In 1922, it was demonstrated that intravenous congo red cleared faster from the blood of patients having significant systemic amyloidosis. In the 1960""s, radiolabeled congo red was used to photometrically determine plasma clearance and in 1962, scientists demonstrated localization of amyloid deposits in the livers and spleens of patients with systemic amyloidosis using nuclear medicine radioimaging techniques and I131-radiolabeled congo red. However, I131 is a radioisotope having a significantly long half-life. Recently, Han et al. disclosed a 99mTc-radiolabeled congo red complex utilizing a bipyridyl analogue (J. Am. Chem. Soc., 118:4506-4507, 1996). Technicium-99m radioisotope has the advantage of a short half-life; however, the bipyridyl analogue of congo red disclosed by Han et al. is apparantly difficult to produce. The present application discloses several 99mTc-radiolabeled congo red complexes and their precursors that utilize one of multiple diamide dithiolate (N2S2) ligand systems conjugated to the Congo red molecule. These 99mTc-radiolabeled congo red complexes and their precursors utilize diamide dithiolate (N2S2) ligand systems that rely upon well defined chemistries and are practical to produce for onsite use. Some of the precursors are suitable for storage as stable salts, and can be complexed with 99mTc when needed.
It is a primary object of the invention to overcome the shortcomings of the prior art radiolabeled congo red complexes by providing a 99mTc-radiolabeled congo red complex that utilizes a diamide dithiolate (N2S2) ligand system.
It is a primary object of the invention to provide a 99mTc-radiolabeled congo red complex utilizing a diamide dithiolate (N2S2) ligand system that is practical to produce.
It is a primary object of the invention to provide a 99mTc-radiolabeled congo red complex utilizing a diamide dithiolate (N2S2) ligand system that is practical to use as a radioimaging agent in warm blooded animals and human patients.
It is a primary object of the invention to provide a 99mTc-radiolabeled Congo red complex utilizing a diamide dithiolate (N2S?) ligand system that is suitable for intravenous or intrathecal administration to a warm blooded animal or human patient.
It is a primary object of the invention to provide a congo red complex precursor utilizing a diamide dithiolate (N2S2) ligand system that forms a stable salt for long term storage and that can be subsequently complexed with 99mTc to form a 99mTc-radiolabeled Congo red complex utilizing a diamide dithiolate (N2S2) ligand system.